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PMID:19822762

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Citation

Etherton, MR, Blaiss, CA, Powell, CM and Südhof, TC (2009) Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc. Natl. Acad. Sci. U.S.A. 106:17998-8003

Abstract

Deletions in the neurexin-1alpha gene were identified in large-scale unbiased screens for copy-number variations in patients with autism or schizophrenia. To explore the underlying biology, we studied the electrophysiological and behavioral phenotype of mice lacking neurexin-1alpha. Hippocampal slice physiology uncovered a defect in excitatory synaptic strength in neurexin-1alpha deficient mice, as revealed by a decrease in miniature excitatory postsynaptic current (EPSC) frequency and in the input-output relation of evoked postsynaptic potentials. This defect was specific for excitatory synaptic transmission, because no change in inhibitory synaptic transmission was observed in the hippocampus. Behavioral studies revealed that, compared with littermate control mice, neurexin-1alpha deficient mice displayed a decrease in prepulse inhibition, an increase in grooming behaviors, an impairment in nest-building activity, and an improvement in motor learning. However, neurexin-1alpha deficient mice did not exhibit any obvious changes in social behaviors or in spatial learning. Together, these data indicate that the neurexin-1alpha deficiency induces a discrete neural phenotype whose extent correlates, at least in part, with impairments observed in human patients.

Links

PubMed PMC2764944 Online version:10.1073/pnas.0910297106

Keywords

Animals; Anxiety; Autistic Disorder/genetics; Behavior, Animal/physiology; Cognition/physiology; Cognition Disorders/etiology; Cognition Disorders/genetics; Cognition Disorders/physiopathology; Electrophysiological Phenomena; Excitatory Postsynaptic Potentials/physiology; Female; Gene Deletion; Grooming/physiology; Hippocampus/physiology; Humans; Learning/physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; Motor Activity/physiology; Neural Cell Adhesion Molecules/deficiency; Neural Cell Adhesion Molecules/genetics; Neural Cell Adhesion Molecules/physiology; Phenotype; Schizophrenia/genetics; Social Behavior; Spatial Behavior/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NRX1B

located_in

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0001225: knockout evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NRX1B

involved_in

GO:0098693: regulation of synaptic vesicle cycle

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

acts_upstream_of

GO:0030534: adult behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

acts_upstream_of

GO:0007612: learning

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

acts_upstream_of

GO:2000821: regulation of grooming behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

involved_in

GO:2000463: positive regulation of excitatory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

involved_in

GO:0051968: positive regulation of synaptic transmission, glutamatergic

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

acts_upstream_of

GO:0050885: neuromuscular process controlling balance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

involved_in

GO:0060134: prepulse inhibition

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1A

located_in

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0001225: knockout evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NRX1A

involved_in

GO:0098693: regulation of synaptic vesicle cycle

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NRX1A

involved_in

GO:2000463: positive regulation of excitatory postsynaptic potential

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q9CS84

P

Seeded From UniProt

complete

HUMAN:NRX1A

involved_in

GO:0051968: positive regulation of synaptic transmission, glutamatergic

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q9CS84

P

Seeded From UniProt

complete

HUMAN:NRX1A

acts_upstream_of

GO:0050885: neuromuscular process controlling balance

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q9CS84

P

Seeded From UniProt

complete

MOUSE:NRX1B

involved_in

GO:0098693: regulation of synaptic vesicle cycle

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NRX1B

part_of

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0001225: knockout evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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